Various models of chromosome structure and function have implicated special classes of nucleotide sequences, especially repeated sequences, as packing principals in chromosome folding, as initiation sites for replication and recombination, and as controlling elements in gene expression and the further processing of transcriptional products. A critical evaluation of such models requires an understanding of the topological relationships between different types of sequences. I wish to analyze sequence organization in the Drosophila genome by partial denaturation mapping in the electron microscope. Alternative ways to generate different kinds of patterns in partially denatured DNA are discussed. Denaturation patterns will be dissected with single- strand specific S1 endonuclease. The ability of DNA fragments to renature or to form folded rings will provide information on the relational spacing of repetitive and non-repetitive sequences. The evolution of topological relationships between sequences will be investigated in mitochondrial DNAs.